Efficacy
In the study by Duvic et al.,r overall response rate (ORR) on the intent-to-treat analysis was 24.2%, with no complete responses (CR) demonstrated. Response rates appeared to be higher in patients who received continuous therapy (31% in group 1, 33% in group 3), compared with group 2 (9%). Median time to response and duration of response were 11.9 and 15.1 weeks, respectively.
In the study by Olsen et al.,r 61% of patients had stage IIB disease or worse, with 40.5% deemed to have Sezary Syndrome. ORR was 29.7%, 1 patient achieving a CR at 281 days of therapy. In patients with at least stage IIB disease, median time to response was 56 days, and median duration of response was not reached (>185 days). Median duration of treatment was 5.3 months, with 61% of patients discontinuing therapy (27 due to progressive disease, 9 due to adverse events, and 25 due to other reasons).
Image 2: Best individual mSWAT score improvement at any visit in patients with at least stage IIB diseaser
© Journal of Clinical Oncology 2007
MAVORICr found superior outcomes for patients treated with mogamulizumab compared to vorinostat. At the time of data cut-off, 110 (59%) of 186 patients assigned to mogamulizumab compared to 131 (70%) of 186 patients assigned to vorinostat had had disease progression or died. Median PFS was 7.7 (5.7-10.3 95% CI) compared to 3.1 (2.9-4.1) in those treated with mogamulizumab versus vorinostat, respectively (hazard ration (HR) 0.53, 95% confidence interval (CI) 0.41-0.69). However, there was no significant difference in OS between the two groups, with median OS not reached with mogamulizumab compared to 43.9 months (43.6-not reached, 95% CI) with vorinostat (HR 0.93, 95% CI 0.61-1.43, p=0.9439). It should be noted that the proportion of patients achieving a response in MAVORIC is markedly lower compared to the trials by Duvic et al.r and Olsen et al.r Possible reasons for this may be due to larger study size as well as different assessment tools.
Image 3: Progression-free survival by investigator assessmentr
© Lancet 2018
Image 4: Hazard ratios for progression-free survival based on investigator assessment in predefined subgroupsr
© Lancet 2018
Study |
Objective response rate
n with event/N (%)
|
Median Time to response (range) in months
|
Duration of response
Median (range) in months
|
Time to progression (TTP) / progression free survival (PFS)
Median in months
|
Overall survival
(months) (95% CI) |
Olsen et al.r |
22/74 (30) |
1.8 (0.9 - 5.7) |
>5.5 (>1.1 - >14.7) |
All: 4.9
CR+PR: >8.5
|
NR |
Duvic et al.r |
8/33 (24) |
2.8 (0.8 - 5.1) |
3.5 (2.2 - 4.5) |
All: 2.8
CR+PR: 7.1
SD: 2.8
PD: 1.2
|
NR |
Kim et al.r |
9/186 (5) |
5.1 (2.9 - 8.5) |
NR |
3.1 (2.9 - 4.1) |
43.9 (0.61 - 1.43) |
n/N = number; CI = confidence interval; CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NR = not reported